Barbaccia M L, Roscetti G, Trabucchi M, Purdy R H, Mostallino M C, Perra C, Concas A, Biggio G
Department of Experimental Medicine, University of Rome Tor Vergata, Italy.
Neuropharmacology. 1996;35(9-10):1299-305. doi: 10.1016/s0028-3908(96)00067-6.
Isoniazid (375 mg/kg, s.c.), a drug that decreases GABAA receptor-mediated transmission, elicited a time-dependent increase of neuroactive steroid (pregnenolone, progesterone and allotetrahydrodeoxycorticosterone) concentrations in rat brain and plasma. This treatment also time-dependently increased the plasma concentration of corticosterone. Brain and plasma neuroactive steroid levels peaked between 40 and 120 min after isoniazid administration, respectively, and returned to control values by 5 hr. Acute foot shock stress mimicked the effect of isoniazid by increasing in a time-dependent manner the same neuroactive steroids both in brain and plasma. Abecarnil (0.3 mg/kg, i.p.), a beta-carboline derivative with anxiolytic properties, antagonized the effect of both isoniazid and foot shock on brain and plasma neuroactive steroids and on plasma corticosterone level. These data indicate that an inhibition of central GABAergic transmission enhances the concentrations of THDOC and its precursors pregnenolone and progesterone in the rat brain and plasma as well as the plasma levels of corticosterone. This finding suggests that GABA exerts a tonic inhibitory action on the mechanisms involved in the regulation of the synthesis and release of these neuroactive steroids in the central nervous system and plasma.
异烟肼（375毫克/千克，皮下注射）是一种可降低GABAA受体介导的神经传递的药物，它可使大鼠脑和血浆中的神经活性甾体（孕烯醇酮、孕酮和别四氢脱氧皮质酮）浓度随时间增加。这种处理还使皮质酮的血浆浓度随时间增加。异烟肼给药后40至120分钟，脑和血浆中的神经活性甾体水平分别达到峰值，并在5小时后恢复到对照值。急性足部电击应激通过使脑和血浆中的相同神经活性甾体随时间增加而模拟了异烟肼的作用。阿贝卡尼（0.3毫克/千克，腹腔注射）是一种具有抗焦虑特性的β-咔啉衍生物，它拮抗了异烟肼和足部电击对脑和血浆神经活性甾体以及血浆皮质酮水平的影响。这些数据表明，中枢GABA能神经传递的抑制会提高大鼠脑和血浆中四氢脱氧皮质酮及其前体孕烯醇酮和孕酮的浓度以及皮质酮的血浆水平。这一发现表明，GABA对中枢神经系统和血浆中这些神经活性甾体的合成和释放调节机制发挥着紧张性抑制作用。
